This invention is directed to pyrimidine-5-carboxamide compounds that act as inhibitors of spleen tyrosine kinase (Syk) and/or JAK kinases. This invention is also directed to pharmaceutical compositions containing the pyrimidine-5-carboxamide compounds and methods of using the compounds or compositions to treat to treat cardiovascular disease, inflammatory disease, autoimmune disease, and/or cell proliferative disorder. The invention is also directed to methods of making the compounds described herein.